1. Field of the Invention
The present invention relates to systems and methods for persistently increasing the overall diameter and the lumen diameter of veins in patients. Specifically, the present invention relates to systems and methods that utilize a blood pump to increase the blood speed and wall shear stress (WSS) on the endothelium of peripheral veins for a period of time that results in a persistent increase in the overall diameter and lumen diameter of those veins.
2. Background Information
Many patients with chronic kidney disease eventually progress to end-stage renal disease (ESRD) and need renal replacement therapy in order to remove fluid and waste products from their body and sustain their life. Most patients with ESRD needing renal replacement therapy receive hemodialysis. During hemodialysis, blood is removed from the circulatory system, cleansed in a hemodialysis machine, and then returned to the circulatory system. Surgeons create discrete “vascular access sites” that can be used to remove and return blood rapidly from ESRD patients. While major advances have been made in the hemodialysis machines themselves and other parts of the hemodialysis process, the creation of durable and reliable vascular access sites where blood can be removed and returned to patients during hemodialysis sessions has seen only modest improvement and remains the Achilles' heel of renal replacement therapy. This often results in sickness and death for ESRD patients and places a large burden on health care providers, payers, and public assistance programs worldwide.
Hemodialysis access sites generally come in three forms: arteriovenous fistulas (AVF), arteriovenous grafts (AVG), and catheters. Each type of site is susceptible to high rates of failure and complications, as described below.
An AVF is constructed surgically by creating a direct connection between an artery and vein. A functional wrist AVF is the longest-lasting, most desirable form of hemodialysis access, with a mean patency of about 3 years. The vein leading away from the connection is called the “outflow” vein. Dilation of the outflow vein is a critical component for an AVF to “mature” and become usable. It is widely believed that the rapid flow of blood in the outflow vein created by the AVF and the WSS it exerts on the endothelium of the vein is the major factor driving vein dilation. Unfortunately, approximately 80% of patients aren't eligible for AVF placement in the wrist, usually due to inadequate vein diameter. For eligible patients where AVF placement is attempted, the site is not usable without further intervention in about 50%-60% of cases, a problem known as “maturation failure”. Small vessel diameter, especially small vein diameter, has been identified as an important factor in AVF maturation failure. The rapid appearance of aggressive vein wall scarring known as “intimal hyperplasia” has also been identified as an important factor in AVF maturation failure. It is generally believed that the turbulence created by the rapid flow of blood out of the artery and into the vein is a major factor causing this vein wall scarring. Some investigators also postulate that cyclic stretching of the vein caused by the entry of pulsatile arterial blood may also play a role in the stimulation of intimal hyperplasia and outflow vein obstruction in AVF. As such, there is a teaching that rapid flow is problematic, and attempts have been made to reduce flow in hemodialysis access sites by restricting lumen diameter by banding in order to minimize failure rates. At the current time, no method exists which preserves positive effects of flow-mediated dilation while eliminating the negative effects of vein wall scarring and obstruction. Not surprisingly, a patient newly diagnosed with ESRD and in need of hemodialysis has only a 50% chance of having a functional AVF within 6 months after starting hemodialysis. Those patients without a functional AVF are forced to dialyze with more costly forms of vascular access and are at a greater risk of complications, sickness, and death.
The second type of vascular access for hemodialysis is known as an arteriovenous graft (AVG). An AVG is constructed by placing a segment of synthetic conduit between an artery and vein, usually in the arm or leg. A portion of the synthetic conduit is placed immediately under the skin and used for needle access. More patients are eligible for AVGs, since veins not visible on the skin surface can be used for outflow, and the rate of early failure is much lower than for AVFs. Unfortunately, AVG mean primary patency is only about 4-6 months, mostly because aggressive intimal hyperplasia and scarring develops rapidly in the wall of the vein near the connection with the synthetic conduit, leading to stenosis and thrombosis. Similar to the situation with AVF failure, the rapid and turbulent flow of blood created by the AVG is thought to drive intimal hyperplasia and scarring in the wall of the outflow vein, often resulting in obstruction of the AVG. Some investigators also postulate that cyclic stretching of the vein caused by the entry of pulsatile arterial blood may also play a role in the formation of intimal hyperplasia and outflow vein obstruction in AVG. Although AVGs are less desirable than AVFs, about 25% of patients dialyze with an AVG, mostly because they are not eligible to receive an AVF.
Patients who are not able to get hemodialysis through an AVF or AVG must have a large catheter inserted in the neck, chest, or leg in order to receive hemodialysis. These catheters often become infected, placing the patient at high risk for sepsis and death. Patients with catheter sepsis usually require hospitalization, removal of the catheter, insertion of a temporary catheter, treatment with IV antibiotics, and then placement of a new catheter or other type of access site when the infection has cleared. Catheters are also susceptible to obstruction by thrombus and fibrin build-up around the tip. Hemodialysis catheters have a mean patency of about 6 months and are generally the least desirable form of hemodialysis access. Although catheters are less desirable than AVFs and AVG, about 20% of patients dialyze with a catheter, mostly because they have not yet been able to receive a functional AVF or AVG, or are not eligible to receive an AVF or AVG.
The problem of hemodialysis access site failure has received more attention recently as the number of ESRD patients undergoing routine hemodialysis has increased worldwide. In 2004, the Centers for Medicare & Medicaid Services (CMS) announced a “Fistula First” initiative to increase the use of AVFs in providing hemodialysis access for patients with end-stage renal failure. This major initiative is a response to published Medicare data showing that patients who dialyze with an AVF have reduced morbidity and mortality compared to patients with an AVG or a catheter. Costs associated with AVF patients are substantially lower than the costs associated with AVG patients in the first year of dialysis, and in subsequent years. The cost savings of a dialyzing with an AVF are even greater when compared to dialyzing with a catheter.
To be eligible for an AVF or AVG, patients must have a peripheral vein with a lumen diameter of at least 2.5 mm or 4 mm, respectively. However, there is currently no method for persistently increasing the overall diameter and lumen diameter of peripheral veins in ESRD patients who are ineligible for an AVF or AVG due to inadequate vein size. Consequently, patients with veins that are too small to attempt an AVF or AVG are forced to use less desirable forms of vascular access such as catheters. Similarly, there is currently no method of treatment for AVF maturation failure, which falls disproportionately on patients with small vein diameters. Thus, systems and methods for enlarging the overall diameter and lumen diameter of a vein prior to the creation of AVF or AVG are needed. The importance of this need is highlighted by a recent study demonstrating that ESRD patients who were forced to use less desirable forms of vascular access such as catheters had a substantially higher risk of becoming sick or dying when compared with patients who were able to use an AVF or AVG for hemodialysis.
There is also a need to persistently increase vein diameter for other patients, such as those with atherosclerotic blockage of peripheral arteries who are in need of peripheral bypass grafting. Patients with peripheral artery disease (PAD) who have an obstruction to blood flow in the arteries of the legs often suffer from claudication, skin ulceration, and tissue ischemia and many of these patients eventually require amputation of portions of the affected limb. In some of these patients, the obstruction can be relieved to an adequate degree by balloon angioplasty or the implantation of a vascular stent. In many patients, however, the obstruction is too severe for these types of minimally invasive therapies. Therefore, surgeons will often create a bypass graft that diverts blood around the obstructed arteries and restores adequate blood flow to the affected extremity. However, many patients in need of a peripheral bypass graft cannot use their own veins as bypass conduits due to inadequate vein diameter and are forced to use synthetic conduits made of materials such as polytetrafluoroethylene (PTFE, e.g. Gore-Tex) or polyethylene terephthalate (PET, e.g. Dacron). Studies have shown that using a patient's own veins as bypass conduits results in better long term patency than using synthetic bypass conduits made from materials such as PTFE or Dacron. The use of a synthetic bypass conduit increases the risk of stenosis in the artery at the distal end of the graft and thrombosis of the entire conduit, resulting in bypass graft failure and a recurrence or worsening of symptoms. Thus, systems and methods for increasing the overall diameter and lumen diameter of veins prior to the creation of bypass grafts are needed, especially for patients who are ineligible to use their own veins for the creation of a bypass graft due to inadequate vein diameter.
In view of the above, it will be apparent to those skilled in the art from this disclosure that there exists a need for a system and method for persistently increasing the lumen diameter and overall diameter of peripheral veins so that those veins can be used for the creation of hemodialysis access sites and bypass grafts. The invention described herein addresses this need in the art as well as other needs, which will become apparent to those skilled in the art from this disclosure.